Transfusion-associated AIDS has become a major health problem as clearly shown by serologic evidence in the general public and by transmission of the disease to chimpanzees with plasma from AIDS patients. The characterization of idiotypic determinants and the generation of anti-idiotypic reagents have provided powerful tools with which to analyze and modulate a given immune response. The idiotype network developed during the course of an immune response provides conceptual insight into the host response to a given antigen. It is proposed to analyze the idiotype network initiated by a host in response to a human T-cell lymphotropic virus type III (HTLV-III) infection or immunization with HTLV-III. The idiotypes that are expressed on human, chimpanzee and mouse antibodies to the envelope glycoproteins, gp 120 and gp 41, of HTLV-III will be examined. The expression of these idiotypic determinants on antibodies to gp 120 and gp 41 produced in naturally infected and immunized individuals will be analyzed. The identification of a major common idiotype(s) in human sera positive for anti-gp 120 and anti-gp 41 will be used to detect potential variable region antibody gene differences among AIDS diagnosed individuals and in blood donors containing antibody but having no disease. The epitopes associated with gp 120 and gp 41 and with synthetic gp 120 and gp 41 peptides will be identified. In addition, we will examine the use of anti-idiotypic antibodies for an effective safe vaccine. The results of these experiments will give insight into whether idiotype networks, expression of particular idiotypes or both are important in the host's response to HTLV-III. These anti-idiotype reagents may also identify serologic markers as indicators of infectivity.